New Concept on Atherogenesis and Treatment of Atherosclerotic Diseases

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"Das initiale fettfreie Ödem" has been long known by the German school as the initial stage of human atherosclerosis, and a highly similar phenomenon was found by the author and his collaborators (1960)14) to be regularly produced as an immediate response to a single administration of atherogenic substances like cholesterol or adrenaline in rabbits and rhesus monkeys. Moreover, the authors found that such an edematous arterial response is induced by a reduction of the active selective-permeability of endothelial cells resulting in an acute infiltration of plasma substances such as β-lipoprotein, fibrinogen and γ-globulin into the arterial wall;10) at the same time, the repelling function of endothelial cells against platelet is reduced.14), 16) As a consequence, the sticking of platelets to endothelial surfaces, as well as the reduction of adhesive platelet count and the shorten-ing of several clotting times due to the release of platelet factors, occur, 14), 16) and ADP-induced platelet aggregability is enhanced.17) When such an impairment of the function of endothelial cells was observed, these cells exhibited a contraction often accompanied by bleb formation. The contraction and blebbing of endothelial cells are proposed to be a key mechanism of atherogenesis and thrombogenesis by the author.To prevent or treat atherosclerosis and thrombosis, a substance capable of preventing or restoring the above mentioned fundamental functions of endothelial cells, and of inhibiting the enhancement of platelet aggre-gability due to atherogenic stress, is essential. One such substance is pyridinolcarbamate, which has also been shown to relax endothelial cells and platelets. This compound has been tested experimentally and clini-cally in many countries of the world for almost 10 years, and a survey of the results of the clinical investigations has been briefly made on its efficacy as an antithrombotic and antiatherosclerotic agent.
International Heart Journal刊行会の論文

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